Fasting Serum Insulin Concentrations Research Articles

Argyreia nervosa Mitigates Insulin Resistance in Liver via IR/IRS-1 Mediated Signaling in Streptozotocin-Induced Type-2 Diabetic Rats

Argyreia nervosa, commonly known as Hawaiian baby woodrose or wooly morning glory, is a plant native to India and is also found in various parts of the world. It is known for its seeds, which have been used traditionally in Ayurvedic and traditional medicine systems for various diseases. The study was aimed at assessing the effect of Argyreia nervosa on insulin signaling molecules of the liver in streptozotocin (STZ)-induced experimental type-2 diabetic rats. Healthy adult male Wistar albino rats -150-180 days old weighing 180-200g was used for the study and divided as Group I - Normal rats; Group II – type-2 diabetic rats; Group III -Diabetic rats + A. nervosa 500 mg/kg b.wt; Group IV-Normal rats + A. nervosa 500 mg/kg b.wt. Fasting blood glucose, and fasting serum insulin were measured by calorimetric methods. Further mRNA expression analysis of insulin receptor (IR) was measured in control and treated animals by quantitative Ream Time PCR analysis. A. nervosa root extract significantly reduced fasting blood glucose and serum insulin concentrations in STZ-induced rats compared with control. In addition, mRNA expression of IR showed a one-fold increase in the expression which shows that A. nervosa is involved in the regulation of insulin signaling in the liver and thereby reduces insulin resistance and type-2 diabetes. Our study concludes that A. nervosa root extract has a significant role on insulin signaling molecules thereby it reduces hyperglycemia and hyperinsulinemia via insulin receptor-mediated pathways. Hence, A. nervosa may be considered as one of the therapeutic natural antidiabetic drugs.

Maternal Obesity Causes Sex Specific Long-Term Hematopoietic and Metabolic Defects

Maternal obesity is increasingly common and can negatively impact offspring health. Children born to obese mothers are at higher risk of developing diseases involved with metabolic health (e.g., type 2 diabetes). Many of these diseases are associated with abnormalities within the hematopoietic system such as atypical immune profiles or hematopoiesis. Interestingly, disease incidence and/or severity is often dependent on the offspring's gender. This suggests that there may be sex-specific reprogramming of hematopoietic stem and progenitor cells (HSPCs) during immune cell development. This study aims to test the hypothesis that offspring of obese mice exhibit sex-differences in HSPC function that affect offspring's metabolic health. To test this, C57BL/6 (CD45.2+) dams were fed standard chow (2018SX, Envigo, IN) or western-style diet (TD.88137, Envigo, IN) for four weeks prior to mating, through pregnancy, and the lactating period. At postnatal day 21, HSPCs (Lineage negative, Sca1 positive, cKit positive cells) were flow-sorted from bone marrow (BM) of offspring from dams fed chow (Con) or western-style diet (MatOb) and used for competitive transplant (Boy/J BM competitor cells; CD45.1+) into same-sex lethally irradiated C57BL/6 x Boy/J F1 (CD45.1+CD45.2+) recipient mice (8-10 weeks of age) or for RNA-sequencing analysis. Secondary transplants were performed to look at long-term engraftment potential of HSPCs. Body weight, body adiposity, fasting insulin, glucose tolerance test (GTT), and pancreatic β and α-cell area were assessed on male and female recipients of both primary and secondary transplants. Compared to mice that received male Con HSPCs, recipient mice that received male MatOb HSPCs had significantly lower donor chimerism in the blood and BM post-secondary transplantation. This was associated with a significant reduction in donor hematopoietic stem cell (HSC) numbers in the BM 16 weeks post-secondary transplant, indicating male MatOb HSPCs had decreased long-term engraftment capability due to an exhaustion of the HSC pool. This reduction in HSPC engraftment seen between male MatOb versus Con HSPCs was not seen when using HSPCs from female offspring. Next, metabolic parameters of our recipient mice was examined. Sixteen weeks after primary transplant, there were no differences detected in body weight and adiposity in the Con and MatOb HSPC recipient mice. Compared to sex-matched controls, we found that recipients transplanted with male MatOb HSPCs developed glucose intolerance, increased fasting serum insulin concentrations, and decreased β-cell area, supporting the presence of impaired glucose metabolism due to a combination of insulin resistance and lower β-cell mass. There was no difference in recipients of HSPCs from female Con and female MatOb pups. RNA-seq of BM HSPCs at time of transplant (p21) from Con or MatOb revealed 100 differentially expressed genes (DEG) in male MatOb HSPCs and 1788 DEG in female MatOb HSPCs. There were more and higher magnitude of differential gene expression in female mice than male, despite the long-term phenotypic differences being evident in males but not females, and the majority of genes changed in males were also altered in females. This suggests that the gene programs responsible for the observed phenotypes may be altered by maternal obesity in both male and female offspring, but that female offspring have a transcriptomic profile that confers protection on the HSPC population. One of the most striking findings from the transcriptomic analysis was a marked enrichment in gene programs associated with immune response, interferon signaling, and cytokine production in female MatOb offspring compared to sex matched controls that is not seen in male MatOb offspring. Pathway analysis identified upregulation of programs involving both IFNγ and IL-10 in the female MatOb HSPCs when compared to sex-mated Con HSPCs which correlated with an increase in IL-10 concentrations in the serum of p21 female MatOb mice. These pathways were downregulated or unaltered in males with no change in systemic IL-10 concentration.Our results demonstrate that maternal obesity results in sex-specific changes in offspring HSPC function and a novel role HSPCs may play in regulating glucose metabolism in the offspring of obese dams.

Fasting plasma insulin in normal-weight apparently healthy adults in a Nigerian population: Reference intervals and influence of age, gender and anthropometric variables

Introduction: In Nigeria, there is paucity of data regarding indigenously established reference intervals for fasting plasma or serum insulin concentrations in the local populations. This study was designed to establish the reference interval of fasting plasma insulin (FPI) among apparently healthy young and middle-aged adults in a Nigerian population. The influence of age, gender, and anthropometric variables on FPI concentration were examined. Materials and Methods: The study was a cross-sectional descriptive study involving 210 reference individuals aged 18 to 64 years. Physical, anthropometric and biochemical variables were measured including FPI and fasting plasma glucose (FPG). The reference interval for FPI was determined using the non-parametric percentile method. Correlation studies between FPI and age, anthropometric indices, and HOMA-IR were carried out. Results: The study involved a total of 210 healthy normal-weight non-diabetic adults consisting of 110 males (52.4%) and 100 females (47.6%) as reference individuals. Reference intervals for FPI for the male, female, and total study participants were 0.1 –11.1mIU/L, 1.3 –13.2mIU/L and 0.1 – 13.03mIU/L respectively. There were statistically significant positive correlations between FPI and age (r = 0.001), WC (r = 0.0.302, p = 0.0001), WHR (r = 0.220, p = 0.0001), SBP (r = 0.137, p = 0.047) FPG (r = 0.165, p = 0.017) and HOMA-IR (r = 0.985, p = 0.0001). Conclusion: The reference interval of FPI using the Biointecho human insulin ELISA kit is 0.1–13.0mIU/L. This is not much at variance with 0.7–9.0mIU/L quoted by the kit manufacturer, but valued widely with that of other commercially available insulin assay kits from different manufacturers. Similar to reports of similar studies, FPI correlated positively with FPG, BMI. WC, BP and age.

Acute insulin response following exercise and its association to lipid changes in sedentary African-American women

Sedentary African-American (AA) women are at increased risk of hypertension, dyslipidemias, metabolic syndrome, and impaired insulin response to exercise. The purpose of the study was to determine the effects of a single bout of aerobic exercise on fasting serum insulin and glucose concentrations following 1464 kJ (350 kcal) of exercise and to determine if this response was associated with serum lipid concentrations in overweight AA women. Premenopausal AA women (n = 11, mean ± SD, age = 32.5 ± 4.8 yr., BMI = 29.8 ± 4.8 kg·m-2, % fat = 35.6 ± 6.3, VO2peak = 21.5 ± 3.6 ml·kg-1·min-1, total cholesterol = 4.8 ± 0.6 mmol·L-1, triglycerides = 0.60 ± 0.2 mmol·L-1, HDLC = 3.3 ± 0.5 mg·dL-1) performed 1464 kJ (350 kcal) of treadmill exercise at 60%-70%VO2peak. Fasting plasma insulin and glucose concentrations were collected 24-h prior to, and immediately, 24-h, and 48 h following exercise. Fasting insulin concentration increased immediately following exercise (Baseline=77.1 ± 10.42 vs. Immediately=117.4 ± 15.28 μU·mL-1, 95%CI= 32.71, 47.89; P<0.05). The change in insulin concentration from 24-h pre- to 24-h post-exercise was correlated with BMI (r= 0.51), VO2peak (r= -0.47), and the change in lipoprotein lipase activity (r=0.37) (P<0.05 for all). In conclusion, in sedentary AA women, the insulin response immediately following exercise may be elevated, and is not suppressed below pre-exercise concentrations during the 48-h following exercise. The insulin response 24-h following exercise is modestly associated with markers of lipoprotein metabolism.

Burden of Cardiovascular Disease in South Asians: Risk Factors Prevention and Early Screening is the Key

Cardiovascular diseases (CVD) have declined over the past two decades.1 However, despite improvements in population health, marked racial and ethnic disparities in longevity and CVD management persist. South Asians (SAs), people with ancestors from the Indian subcontinent constitute 1/5 of the world's population. During the late 1980s, the term “double burden of disease” was first used and can be defined as the burden of non-communicable diseases on top of infectious diseases that remain undefeated.2 Coronary artery disease (CAD), also called heart disease, stood out as the most common cause of this increasing double burden of diseases. The first study that was published related to South Asians and CAD risk was in 1991 by McKeigue et al.3 The study assessed the relation of central obesity and insulin resistance with high type 2 diabetes mellitus prevalence and CAD risk in immigrant SAs. A sample of industrial workers and general practitioners in the United Kingdom were shown to have a higher prevalence of diabetes, higher blood pressure, higher fasting and post-glucose serum insulin concentrations, higher plasma triglyceride (TG), and lower high-density lipoprotein (HDL). This study confirms the existence of an insulin resistance syndrome in SAs.

Elevated miR-143 and miR-34a gene expression in human visceral adipose tissue are associated with insulin resistance in non-diabetic adults: a cross-sectional study.

We aimed to evaluate the association of miR-143 and miR-34a expression in human visceral (VAT) and subcutaneous (SAT) adipose tissues with insulin resistance (IR). VAT and SAT were obtained from 176 participants without diabetes. miR-143 and miR-34a expressions in VAT and SAT were measured using qRT-PCR.Fasting serum insulin and glucose concentration, homeostatic model assessment of IR index (HOMA-IR) and β-cell function (HOMA-B), and quantitative insulin-sensitivity check index (QUICKI) were calculated. After adjustment for age, sex and body mass index (BMI), VAT miR-143 expression was positively associated with fasting plasma glucose (FPG), insulin, and HOMA-IR, and negatively associated with HOMA-Band QUICKI. miR-34a expression in VAT was directly associated with FPG, insulin, and HOMA-IRand negatively associated with QUICKI. In SAT, miR-34a expression was positively associated with insulinand negatively associated with QUICKI. The interaction terms of HOMA-IR and BMI categories were significant for both miR gene expressions in VAT. After stratifying participants based on BMI, the association of miR-143 and miR-34a expressions in VAT with IR indices remained significant only in obese patients. miR-143 and miR-34a expressions in VAT were independent predictors of IR in people without diabetes, and that this association was conditional on the degree of obesity. Level of evidence III, cross-sectional analytic study.

The Impact of Nutritional Supplementation During Pregnancy on the Incidence of Gestational Diabetes and Glycaemia Control.

The nutritional state before and throughout pregnancy has a critical impact on the women's health and the baby's development and growth. The release of placental hormones during pregnancy induces/ increases maternal insulin resistance and promotes nutrition utilization by the fetus. Gestational Diabetes Mellitus (GDM) is the most common medical complication in pregnancy and is associated with significant maternal and fetal morbidity. Several studies have examined the effect of physical activity, healthy eating, and various food supplements on the risk of developing gestational diabetes (GDM) and related outcomes. Among those, Myo-Inositol supplementation has shown encouraging results in the prevention of GDM. Maternal vitamin D deficiency has been associated with an elevated risk of GDM, and supplementation can improve glucose haemostasis by lowering fasting blood glucose, HbA1c, and serum insulin concentration. Probiotics modulate the gut microbiota leading to an improved glucose and lipid metabolism, which is proposed to reduce the risk of GDM. We aim to review the strength and limitation of the current evidence for using some nutritional supplements either as single agents or in combinations on the risk of developing GDM and on glycaemic control.

Development and validation of dietary and lifestyle insulinemic indices among Iranian adult population

BackgroundThere is no study regarding developing a valid index to predict insulin-related disorders in the Iranian population based on their dietary habits and lifestyle. In the current study, we aimed to develop and validate insulinemic potential indices of diet and lifestyle in Iranian adults.MethodsIn this cross-sectional study, we analysed data of 1063 men and women aged ≥ 25 years among participants of the examination three of Tehran lipid and glucose study (TLGS) (2006–2008). Dietary intakes were assessed using a valid semi-quantitative food frequency questionnaire. Dietary and lifestyle indices were developed using stepwise linear regression analysis based on dietary intakes, body mass index, and physical activity data. Fasting serum insulin concentration and homeostatic model assessment for insulin resistance (HOMA-IR) were used as biomarkers of hyperinsulinemia (HI) and insulin resistance (IR). Validation analyses were performed in examination four of TLGS.ResultsWe developed four indices related to insulin homeostasis, including the dietary index for HI (DIH), the dietary index for IR (DIR), the lifestyle index for HI (LIH), and the lifestyle index for IR (LIR). Based on multivariable-adjusted models, the relative values of the biomarker in subjects in the highest quartile of indices were 45% for LIH (95% CI 1.36–1.55, Ptrend < 0.001), 28% for DIR (95% CI 1.13–1.42, Ptrend = 0.019), and 51% for LIR (95% CI 1.41–1.61, Ptrend < 0.001), higher than those in the reference quartile, respectively.ConclusionWe designed and validated indices to determine the insulin potential of diet and lifestyle for the Iranian population, according to Iran’s demographic and dietary intake characteristics.

Prenatal androgen excess impairs beta-cell function by decreased sirtuin 3 expression.

Prenatal androgen exposure induces metabolic disorders in female offspring. However, the long-term effect of maternal testosterone excess on glucose metabolism, especially on pancreatic beta-cell function, is rarely investigated. Our current study mainly focused on the effects of prenatal testosterone exposure on glucose metabolism and pancreatic beta- cell function in aged female offspring. By using maternal mice and their female offspring as animal models, we found that prenatal androgen treatment induced obesity and glucose intolerance in aged offspring. These influences were accompanied by decreased fasting serum insulin concentration, elevated serum triglyceride, and testosterone concentrations. Glucose stimulated insulin secretion in pancreatic beta cells of aged female offspring was also affected by prenatal testosterone exposure. We further confirmed that increased serum testosterone contributed to downregulation of sirtuin 3 expression, activated oxidative stress, and impaired pancreatic beta-cell function in aged female offspring. Moreover, over-expression of sirtuin 3 in islets isolated from female offspring treated with prenatal testosterone normalized the oxidative stress level, restored cyclic AMP, and ATP generation, which finally improved glucose-stimulated insulin secretion in beta cells. Taken together, these results demonstrated that prenatal testosterone exposure caused a metabolic disturbance in aged female offspring via suppression of sirtuin 3 expression and activation of oxidative stress in pancreatic beta cells.

Vitamin D Supplementation Improves Fasting Insulin Levels and HDL Cholesterol in Infertile Men

Vitamin D has been linked with glucose and lipid metabolism. Men with impaired gonadal function have a higher risk of metabolic syndrome and mortality, and vitamin D status may be a reversible modulator. This work aimed to determine the effect of daily vitamin D and calcium supplementation for 150 days on glucose and lipid homeostasis in infertile men. A single-center, double-blinded, randomized clinical trial (NCT01304927) was conducted. A total of 307 infertile men were randomly assigned (1:1) to a single dose of 300 000 IU cholecalciferol followed by 1400 IU cholecalciferol + 500 mg of calcium daily (n = 151) or placebo (n = 156) for 150 days. Reported metabolic parameters including fasting plasma glucose, glycated hemoglobin A1c, fasting serum insulin, homeostatic model assessment of insulin resistance (HOMA-IR), fasting plasma cholesterols, and triglycerides were secondary end points. The primary end point semen quality has previously been reported. Men receiving vitamin D supplementation improved their vitamin D status, whereas vitamin D status was aggravated in the placebo group characterized by higher serum parathyroid hormone. At the end of the trial, men receiving vitamin D supplementation had 13% lower fasting serum insulin concentrations compared with the placebo-treated group (65 vs 74 pmol/L, P = .018) and 19% lower HOMA-IR (2.2 vs 2.7, P = .025). Moreover, men in the vitamin D group had higher high-density lipoprotein (HDL) cholesterol levels (1.38 vs 1.32 mmol/L, P = .008) compared with the placebo group. High-dose vitamin D supplementation has beneficial effects on glucose homeostasis and HDL cholesterol levels in infertile men.

Diagnostic Power of Circulatory Metabolic Biomarkers as Metabolic Syndrome Risk Predictors in Community-Dwelling Older Adults in Northwest of England (A Feasibility Study).

Background: Metabolic Syndrome (MetS) is a cluster of risk factors for diabetes and cardiovascular diseases with pathophysiology strongly linked to aging. A range of circulatory metabolic biomarkers such as inflammatory adipokines have been associated with MetS; however, the diagnostic power of these markers as MetS risk correlates in elderly has yet to be elucidated. This cross-sectional study investigated the diagnostic power of circulatory metabolic biomarkers as MetS risk correlates in older adults. Methods: Hundred community dwelling older adults (mean age: 68.7 years) were recruited in a study, where their blood pressure, body composition and Pulse Wave Velocity (PWV) were measured; and their fasting capillary and venous blood were collected. The components of the MetS; and the serum concentrations of Interleukin-6 (IL-6), Tumor Necrosis Factor-α (TNF-α), Plasminogen Activator Inhibitor-I (PAI-I), Leptin, Adiponectin, Resistin, Cystatin-C, C-Reactive Protein (CRP), insulin and ferritin were measured within the laboratory, and the HOMA1-IR and Atherogenic Index of Plasma (AIP) were calculated. Results: Apart from other markers which were related with some cardiometabolic (CM) risk, after Bonferroni correction insulin had significant association with all components of Mets and AIP. These associations also remained significant in multivariate regression. The multivariate odds ratio (OR with 95% confidence interval (CI)) showed a statistically significant association between IL-6 (OR: 1.32 (1.06–1.64)), TNF-α (OR: 1.37 (1.02–1.84)), Resistin (OR: 1.27 (1.04–1.54)) and CRP (OR: 1.29 (1.09–1.54)) with MetS risk; however, these associations were not found when the model was adjusted for age, dietary intake and adiposity. In unadjusted models, insulin was consistently statistically associated with at least two CM risk factors (OR: 1.33 (1.16–1.53)) and MetS risk (OR: 1.24 (1.12–1.37)) and in adjusted models it was found to be associated with at least two CM risk factors and MetS risk (OR: 1.87 (1.24–2.83) and OR: 1.25 (1.09–1.43)) respectively. Area under curve (AUC) for receiver operating characteristics (ROC) demonstrated a good discriminatory diagnostics power of insulin with AUC: 0.775 (0.683–0.866) and 0.785 by cross validation and bootstrapping samples for at least two CM risk factors and AUC: 0.773 (0.653–0.893) and 0.783 by cross validation and bootstrapping samples for MetS risk. This was superior to all other AUC reported from the ROC analysis of other biomarkers. Area under precision-recall curve for insulin was also superior to all other markers (0.839 and 0.586 for at least two CM risk factors and MetS, respectively). Conclusion: Fasting serum insulin concentration was statistically linked with MetS and its risk, and this link is stronger than all other biomarkers. Our ROC analysis confirmed the discriminatory diagnostic power of insulin as CM and MetS risk correlate in older adults.

Dietary Selenium Requirement for the Prevention of Glucose Intolerance and Insulin Resistance in Middle-Aged Mice.

Although dietary selenium (Se) deficiency or excess induces type 2 diabetes-like symptoms in mice, suboptimal body Se status usually causes no symptoms but may promote age-related decline in overall health. We sought to determine the dietary Se requirement for protection against type 2 diabetes-like symptoms in mice. Thirty mature (aged 4 mo) male C57BL/6J mice were fed a Se-deficient torula yeast AIN-93M diet supplemented with Na2SeO4 in graded concentrations totaling 0.01 (basal), 0.04, 0.07, 0.10, and 0.13 (control) mg Se/kg for 4 mo (n=6) until they were middle-aged (8 mo). Droplets of whole blood were used to determine glucose tolerance and insulin sensitivity in the mice from ages 5 to 8 mo. Postmortem serum, liver, and skeletal muscle were collected to assay for selenoprotein expression and markers of glucose metabolism. Data were analyzed by 1-way ANCOVA with or without random effects for time-repeated measurements using live mice or postmortem samples, respectively. Compared with control, the consumption of basal diet increased (P<0.05) fasting serum insulin (95% CI: 52%, 182%) and leptin (95% CI: 103%, 118%) concentrations in middle-aged mice. Dietary Se insufficiency decreased (P<0.05) 1) glucose tolerance (13-79%) and insulin sensitivity (15-65%) at ≤0.10 mg Se/kg; 2) baseline thymoma viral proto-oncogene phosphorylation on S473 (27-54%) and T308 (22-46%) at ≤0.10 and ≤0.07 mg Se/kg, respectively, in the muscle but not the liver; and 3) serum glutathione peroxidase 3 (51-83%), liver and muscle glutathione peroxidase 1 (32-84%), serum and liver selenoprotein P (28-42%), and liver and muscle selenoprotein H (39-48%) and selenoprotein W (16-73%) protein concentrations at ≤0.04, ≤0.10, ≤0.07, and ≤0.10 mg Se/kg, respectively. Mice fed diets containing ≤0.10 mg Se/kg display impaired glucose tolerance and insulin sensitivity, suggesting increased susceptibility to type 2 diabetes by suboptimal Se status at levels ≤23% of nutritional needs.

Homeostasis model assessment, serum insulin and their relation to body fat in cats

BackgroundObesity is associated with insulin resistance (IR) and considered a risk factor for diabetes mellitus (DM) in cats. It has been proposed that homeostasis model assessment (HOMA-IR), which is the product of fasting serum insulin (mU/L) and glucose (mmol/L) divided by 22.5, can be used to indicate IR. The objectives of this study were threefold: (i) to evaluate associations between body fat, fasting insulin, and HOMA-IR, (ii) to determine population-based reference interval of HOMA-IR in healthy lean cats, and (iii) to evaluate biological variation of HOMA-IR and fasting insulin in cats.Results150 cats were grouped as lean or overweight based on body condition score and in 68 of the cats body fat percentage (BF%) was estimated by computed tomography. Fasting serum insulin and glucose concentrations were analysed. Statistical differences in HOMA-IR and insulin between overweight or lean cats were evaluated using Wilcoxon rank-sum test. Robust method with Box-Cox transformation was used for calculating HOMA-IR reference interval in healthy lean cats. Relations between BF% and HOMA-IR and insulin were evaluated by regression analysis. Restricted maximum likelihood ratio was used to calculate indices of biological variation of HOMA-IR and insulin in seven cats.There were significant differences between groups with overweight cats (n = 77) having higher HOMA-IR (p < 0.0001) and insulin (p = 0.0002) than lean cats (n = 73). Reference interval for HOMA-IR in lean cats was 0.1–3.0. HOMA-IR and fasting insulin concentrations showed similar significant positive association with BF% (p = 0.0010 and p = 0.0017, respectively). Within-animal coefficient of variation of HOMA-IR and insulin was 51% and 49%, respectively.ConclusionsHOMA-IR and fasting insulin higher in overweight than lean cats and correlate to BF%. The established population-based reference interval for HOMA-IR as well as the indices of biological variation for HOMA-IR and fasting insulin may be used when interpreting HOMA-IR and fasting insulin in cats. Further studies are needed to evaluate if HOMA-IR or fasting insulin is useful for identifying cats at risk of developing DM.

Immunotherapy against angiotensin II receptor ameliorated insulin resistance in a leptin receptor-dependent manner.

The angiotensin II type 1 receptor (AT1R) signaling pathway is reported to modulate glucose metabolism. Targeting AT1R, our group invented ATRQβ-001 vaccine, a novel immunotherapeutic strategy to block the activation of AT1R. Here, we evaluated the therapeutic efficacy of ATRQβ-001 vaccine in insulin resistance, and investigated the mechanism. Our results showed that ATRQβ-001 vaccine and specific monoclonal antibody against epitope ATR-001 (McAb-ATR) decreased fasting serum insulin concentration and improved glucose and insulin tolerance in ob/ob mice. These beneficial effects were verified in high-fat diet-induced obese mice. McAb-ATR activated insulin signaling in skeletal muscle and insulin-resistant C2C12 myotubes without affecting liver or white adipose tissue of ob/ob mice. Mechanistically, the favorable impact of McAb-ATR on insulin resistance was abolished in db/db mice and in C2C12 myotubes with leptin receptor knockdown. AT1R knockdown also eradicated the effects of McAb-ATR in C2C12 myotubes. Furthermore, McAb-ATR treatment was able to activate the leptin receptor-mediated JAK2/STAT3 signaling in skeletal muscle of ob/ob mice and C2C12 myotubes. Additionally, angiotensin II downregulated the leptin signaling in skeletal muscle of ob/ob and diet-induced obese mice. We demonstrated that ATRQβ-001 vaccine and McAb-ATR improved whole-body insulin resistance and regulated glucose metabolism in skeletal muscle in a leptin receptor-dependent manner. Our data suggest that immunotherapy targeting AT1R is a novel strategy for treating insulin resistance.

Long-term nitrate administration increases expression of browning genes in epididymal adipose tissue of male type 2 diabetic rats

Expression of browning genes are lower in both humans and animals with type 2 diabetes (T2D). This study aims at determining effects of long-term nitrate administration on protein and mRNA levels of uncoupling protein 1 (UCP1), peroxisome proliferator activated receptor gamma (PPAR-γ), and PPAR-γ coactivator 1 alpha (PGC1-α) in epididymal adipose tissue (eAT) of rats with T2D. Male Wistar rats were divided into 4 groups (n = 6/group): Control, diabetes, control + nitrate (CN), and diabetes + nitrate (DN). T2D was induced using high fat diet combined with a low-dose of streptozotocin (30 mg/kg body weight). Sodium nitrate was administrated at a dose of 100 mg/L for 6 months in nitrate-treated rats. Fasting serum glucose and insulin concentrations were measured at months 0 (i.e. at start of the protocol), 3, and 6. At month 6, protein and mRNA levels of UCP1, PPAR-γ, and PGC1-α were measured in eAT samples. In addition, tissue concentration of cyclic guanosine monophosphate (cGMP) was measured and histological analyses were done at month 6. In rats with T2D, 6-month administration of nitrate decreased serum glucose and insulin concentrations by 13% and 23%, respectively and increased cGMP level by 85%. Rats with T2D had lower mRNA and protein levels of PPAR-γ (62%, P < 0.0001 and 18%, P = 0.0472), PGC1-α (49%, P = 0.0019 and 21%, P = 0.0482), and UCP1 (35%, P = 0.0613 and 30%, P = 0.0031) in eAT; 6-month nitrate administration restored these decreased levels to near control values. In addition, nitrate increased adipocyte density by 193% and decreased adipocyte area by 53% in rats with T2D. In conclusion, long-term low-dose nitrate administration increased mRNA and protein expressions of browning genes in white adipose tissue of male rats with T2D; these findings partly explain favorable metabolic effects of nitrate administration in diabetes.

Preliminary evidence of insulin resistance in young adults with impaired sleep

Objective Impaired sleep is associated with insulin resistance (IR), a precursor to type 2 diabetes mellitus (T2DM), but is poorly understood in young adults. This cross-sectional study examined sleep characteristics, risk factors for T2DM, and IR in college students. Participants: Thirty-two college students (18–25 years) with either short sleep or poor quality sleep were assessed. Methods: Participants completed self-report measures of sleep and T2DM risk factors. One week of objective sleep was measured with wrist actigraphy. IR was calculated from fasting serum glucose and insulin concentrations. Results: The sample slept on average 6.6 hours/night, and over half had IR. Of those with IR, 44.4% had normal body mass index (BMI), 72% had normal fasting glucose concentrations, and all but one had T2DM risk test score indicating they were not at risk. Conclusions: IR was found in over half of participants; however, many typical T2DM risk factors were not present in those with IR.

Dynamic changes of blood glucose, serum biochemical parameters and gene expression in response to exogenous insulin in Arbor Acres broilers and Silky fowls

Silky chicken is a breed of chickens with black skin and slow growth rate used in Chinese traditional medicine, whereas Arbor Acres broiler is a well-known commercial breed in the poultry industry, it is featured by a large size, rapid-growth rate, high feed-conversion rate and strong adaptability. The difference in their rate of growth may be primarily related to different mechanism for glucose metabolism. Here we compared the insulin sensitivity of the two breeds; we investigated the temporal changes (at 0 min, 120 min and 240 min) of serum insulin and other biochemical parameters and determined the spatio-temporal changes of gene mRNA abundance in response to exogenous insulin (80 μg/kg body weight). The results indicated that: (1) Silky chickens showed stronger blood glucose recovery than broilers in the insulin resistance test. (2) The serum urea level in Silky chickens was twice of broilers; exogenous insulin significantly up-regulated serum uric acid level in Silky fowls in a time-dependent manner and increased serum cholesterol content at 120 min. (3) Two breeds showed distinctly different temporal changed in serum insulin in response to exogenous insulin stimulation. The fasting serum insulin concentration of broilers was three-fold of Silky chickens at the basal state; it decreased significantly after insulin injection and the levels at 120 min and 240 min of broilers were only 23% (P < 0.01) and 14% (P < 0.01) of the basal state, respectively. Whereas the serum insulin content in Silky chickens showed stronger recovery, and the 240 min level was close to the 0 min level. (4) GLUT2, GLUT12, neuropeptide Y and insulin receptor (IR) were predominantly expressed in the liver, pectoralis major, olfactory bulb and pancreas, respectively, where these genes presented stronger insulin sensitivity. In addition, the IR mRNA level was strongly positively with the GLUT12 level. In conclusion, our findings suggested that Silky chickens have a stronger ability to regulate glucose homeostasis than broilers, owing to their higher IR levels in the basal state, stronger serum insulin homeostasis and candidate genes functioning primarily in their predominantly expressed tissue in response to exogenous insulin.

Zengye Decoction Ameliorates Insulin Resistance by Promoting Glucose Uptake.

The incidence of type 2 diabetes mellitus (T2DM) has been increasing in recent years and has become a serious threat to human health. Zengye Decoction (ZYD), a well-known traditional Chinese medicinal formula, has been used in the treatment of T2DM with yin asthenia and extreme heat since Qing Dynasty. However, the characteristics of antidiabetic activities of ZYD have not been fully elucidated. In our study, high-fat diet and streptozotocin were used to establish the T2DM rat model. After 3 weeks of treatment with ZYD, the fasting blood glucose (FBG), oral glucose tolerance, the fasting serum insulin concentration, insulin sensitivity index (ISI), serum lipid profiles, and pancreas histopathology were measured. Then, under circumstance of insulin-resistant glucose consumption, 2-(N-(7-nitrobenz-2-oxa-l,3-diazol-4-yl) amino)-2-deoxyglucose (2-NBDG) uptake and glycogen content in C2C12 myotubes, 3T3-L1 adipocytes, and HepG2 cells were determined, respectively. Finally, the expressions of key targets in the insulin signaling pathway were measured to explain the potential mechanism underlying these activities. After administration with ZYD, a notable reduction in FBG levels, oral glucose tolerance test-area under the curve, blood lipid metabolism, and ISI values were observed compared with the diabetic control group. Moreover, ZYD restored the damaged islet cells in T2DM rats. Significant increases in glucose consumption, glucose uptake, glycogen content, expression of glucose transporter type 4, and the ratio of p-Akt/Akt were observed in the ZYD groups. According to the above results, ZYD exhibited glucose disposal, including glucose consumption, glucose uptake, and glycogen content and promoted the Akt signal pathway, which indicates that ZYD exerts significant hypoglycemic effect in T2DM.

843 A Study on Changes of Pancreatic Structure and Function After Severe Burns and Its Mechanism

Abstract Introduction This research was to explore the changes of pancreatic structure and function after severe burns and its mechanism. Methods A scald model of rats with a 50% total body surface area was established. Rats were injected with bpv (hopic, 0.6 mg/kg) subcutaneously once daily post scald creation. Rats’ fasting blood glucose (FBG) and serum insulin concentration were measured to calculate the insulin resistance index at 72 h post injury. Western blot assay was used to measure the content of p-Akt and t-Akt in pancreatic tissue and observe Akt phosphorylation levels. Paraffin sections and electron microscopic sections of pancreatic tissue were prepared for observation under light and transmission electron microscopy. The number of insulin particles and insulin vacuoles attached to per 10 μm of the cell membrane in β cells were calculated. Results Scalds increased FBG and impaired glucose tolerance significantly in the rats. Bpv could reduce blood glucose and improve glucose tolerance remarkably. Western blot assay revealed that the activity of PI3k/Akt pathway in rats’ pancreas decreased after scalding, and bpv could up-regulate its activity. The number of insulin particles attached to to per 10 μm of the cell membrane in β cells was reduced, and the proportion of insulin vacuoles was increased, indicating that rats’ insulin secretion function was impaired. After treatment with bpv, rats’ insulin secretion function was improved. Conclusions The activity of PI3k/Akt pathway in scalded rats’ pancreas is reduced and the insulin secretion function is decreased. Improving the activity of PI3k/Akt pathway in rats’ pancreas may improve the insulin secretion function and restore physiological blood glucose levels during the early stage after scalding. Applicability of Research to Practice This research may be applicable in practice in the future to regulate the metabolism of burn patients.

GLP-1 signaling is required for improvement of glucose tolerance by osteocalcin.

Osteocalcin is a bone-derived hormone that in its uncarboxylated form (GluOC) plays an important role in glucose and energy metabolism by stimulating insulin secretion and pancreatic β-cell proliferation through its putative receptor GPRC6A. We previously showed that the effect of GluOC on insulin secretion is mediated predominantly by glucagon-like peptide-1 (GLP-1) released from intestinal endocrine cells in response to GluOC stimulation. Moreover, oral administration of GluOC was found to reduce the fasting blood glucose level, to improve glucose tolerance, and to increase the fasting serum insulin concentration and β-cell area in the pancreas in wild-type mice. We have now examined the effects of oral GluOC administration for at least 4 weeks in GLP-1 receptor-knockout mice. Such administration of GluOC in the mutant mice triggered glucose intolerance, enhanced gluconeogenesis and promoted both lipid accumulation in the liver as well as adipocyte hypertrophy and inflammation in adipose tissue. Furthermore, inactivation of GLP-1 receptor signaling in association with GluOC administration induced activation of the transcription factor FoxO1 and expression of its transcriptional coactivator PGC1α in the liver, likely accounting for the observed upregulation of gluconeogenic gene expression. Our results thus indicate that the beneficial metabolic effects of GluOC are dependent on GLP-1 receptor signaling.